Study of the neuroprotective effects of BDNF, bFGF, CNTF or several doses of PEDF in a focal Light-emission-diode (LED) - induced phototoxicity model in adult albino mice

Abstract

Purpose : To investigate the neuroprotective effects of the trophic factors Brain-derived-neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) or different doses of purified human recombinant pigment epithelium-derived factor (PEDF), in a LED induced phototoxicity (LIP) photoreceptor degeneration model.

Methods : Adult female Swiss mice (25-35 g) were dark adapted overnight, anesthetized and their left pupil dilated with topical tropicamide (1%). A 10V blue (400nm) LED was placed at 1mm from the cornea and the eye exposed for 20 seconds (200lux). LIP damage was assessed in retinas immunodetected 7 days after LIP against S-opsin, which identifies approximately 96% of the entire cone population in the adult albino mice (Ortín-Martínez et al., 2014 PONE 8:131). The effects of a single intravitreal injection, immediately after LIP, of BDNF (2.5µg), CNTF (0.2µg), PEDF (0.1, 0.3 or 0.5µg) or bFGF (0.5µg) in the S-cone population were examined on flat-mounted retinas at 7 days. Total numbers of S-cones were counted automatically within a circular area (with a radius of 0.4 mm) centered on the lesion in the left retinas and in a corresponding region of their fellow right retinas, which served as controls.

Results : Wholemounts showed a circular region located in the superotemporal quadrant, at approximately 0.8 mm from the optic disk, with diminished numbers of S-cones. In this area the number of S-cones were 2,074±380 (n=8) for the LED exposed retinas treated with PBS while there were 5,716±550 (n=8) in the contralateral fellow retinas, indicating a survival of approximately 36% of the original population. The following intravitreal treatments resulted in significant neuroprotective effects with greater survival on the S-cone population, when compared with their corresponding vehicle groups: BDNF (56%; n=8), bFGF (50%; n=8), PEDF 0.5µg (53%, n=8). However CNTF (40%; n=7), PEDF 0.3 µg (38%; n=7) and PEDF 0.1 µg (37%; n=7) did not show a significant protection.

Conclusions : The focal loss of cones caused by LIP in the albino mouse retina is a reliable model that can be rescued significantly with a single intravitreal administration of BDNF, PEDF or bFGF.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.